Previous studies have shown that weight loss results in loss of bone mineral density (BMD), but it is unknown whether this loss translates into increased osteoporotic fracture risk. The current gold standard for assessing BMD is dual energy X-ray absorptiometry (DXA). DXA does not isolate changes in cortical and trabecular bone, which may be differentially affected by changes in weight. Quantitative computed tomography (OCT) provides the distinct advantage of measuring true volumetric BMD (vBMD) for both cortical and trabecular compartments, which are key determinants of bone strength and fracture resistance. To our knowledge, there are no published studies of changes in vBMD in response to weight loss. The proposed project will evaluate the effects of exercise-induced weight loss in postmenopausal women on lumbar spine (LS) and femoral neck (FN) vBMD and determine the potential mediators (e.g., estrogen, insulin-like growth factor-1 (IGF-1), Cortisol and leptin) that influence changes in LS and FN vBMD. We hypothesize that 1) compared with weight stable controls, women undergoing exercise-induced weight loss will have significantly larger decreases in both trabecular and cortical LS and FN vBMD as assessed by OCT. Further, the decrements in trabecular vBMD will exceed changes in cortical vBMD and 2) the change in trabecular and cortical LS and FN vBMD following exercise-induced weight loss will be directly associated with changes in body mass, IGF-1, estrogen and leptin but inversely associated with changes in Cortisol and serum bone turnover makers. The purpose of this study is to examine the impact of exercise-induced weight loss on different bone compartments (cortical vs. trabecular) and bone architecture in healthy postmenopausal women. The information gained from this research will lay the groundwork for future studies examining the long-term sequelae of decreased cortical and trabecular bone. Ultimately, we hope to better understand what causes such bone changes as it is unknown whether this puts women at increased risk for osteoporotic fracture.